Effects of magnesium and its mechanism on the incidence of reperfusion arrhythmias following severe ischemia in isolated rat hearts

Magnesium sulfate (Mg) has been widely used for the treatment of ventricula r arrhythmias (VF) in patients with coronary artery disease. However, the m echanisms of prevention on the incidence of VF have not been defined. The a im of study was to investigate the role of Mg in the prevention of VF and t he mechanism of those effects. Series I studied antiarrhythmic effects on V F. isolated rat hearts were perfused in the working heart mode with Krebs'- Henseleit bicarbonate buffer (KHB). Whole heart ischemia was induced by a o ne-way ball. valve with 300 beats/min electrical pacing for 10 minutes foll owed by 20 minutes of aerobic reperfusion. After control perfusion, Mg was added from 5 minutes before ischemia and was continued to the end of ischem ia (1.2 mM for the control group and 2.4, 3.6, 4.8, and 9.6 mM for the stud y animals) or during reperfusion (3.6 mM). Left ventricular pressure, aorti c flow and ECG were monitored. Series 2 studied the effect of Mg on [Ca2+]i . Hearts were perfused by the Langendorff mode and mere loaded with 4 muM o f Fura 2/AM. as a [Ca2+]i indicator. Ca2+ was monitored using the ratio of Fura-2 fluorescence intensity at excitation wavelengths of 340 and 380 nm. The hearts were subjected to a 20 minutes of low-flow ischemia followed by 20 minutes of aerobic reperfusion. Then 3.6 mM Mg was added to the KHB medi um during ischemia. The duration of VF was significantly suppressed in the 2.4, 3.6, and 4.8 mM/L Mg-added groups (472 +/- 173, 779 +/- 159, and 525 /- 202 second, respectively) when compared with the control group (1200 sec onds). Magnesium sulfate suppressed the fluorescence ratio of the diastolic Ca2+ level at the end of 20 minutes of ischemia from 40.5 +/- 3.6% to 9.0 +/- 1.0% (P < 0.05 vs, control hearts). These results suggested that Mg had a beneficial effect on VF and that the optimal Mg concentration was betwee n 2.4 and 4.8 mM. The mechanism of the prevention of VF by Mg could be thro ugh the inhibition of [Ca2+]i retention during ischemia.